Eyes are an important sensory organ of the human body. More than 70% of the external information obtained by the human brain comes from vision. According to statistics, in 2019, a total of 710 million people in the world suffered from various forms of eye diseases, and with the growth and aging of the population, the number of patients with eye diseases is still rising significantly. Eye diseases can be divided into six types: glaucoma, cataract, age-related macular degeneration, refractive eye disease, near vision loss, and other vision loss. The factors that cause eye diseases are related to systemic diseases. The treatment of eye diseases is very important, if left untreated, it can cause further damage and even blindness.
Deuterium is a stable, safe and non-radioactive hydrogen isotope that has been widely used in human metabolism and clinical research. Deuterated compounds are not only widely used as human metabolic and pharmacokinetic probes, but also as real drugs to treat eye diseases.
The non-enzymatic synthesis of A2E in the retina involves cleavage of the C20-H bond in single-bond retinal-PE, and the binding of deuterium to vitamin A at the C20-H position stabilizes the C20-D bond and inhibits A2E production. Demonstration of the efficacy of deuterated derivatives of vitamin A in animal models requires complete replacement of natural forms of vitamin A with their deuterated analogs. Given the lack of mechanism-based side effects expected from other classes of drugs that inhibit lipofuscin formation, such as direct visual cycle inhibitors, C20-D3 therapy represents a potentially attractive approach to inhibit retinal bis-retinoic acid formation.
(R)-Emixustat, derived from retinamine, is currently in clinical development as a potent retinol isomerase inhibitor. Effective use of Emixustat is complicated because it is rapidly metabolized, limiting the duration of its pharmacological action. The regioselective incorporation of deuterium can effectively prolong the activity of emixustat in vivo. By measuring the distribution and retention of both compounds in the mouse eye, levels of deuterated emixustat were found to be approximately twice that of emixustat, suggesting that deuteration may have a positive effect on ocular drug retention.
Fig.1 Scheme showing the oxidation of emixustat or 58 (2H-emixustat) by VAP-1 present in the aorta homogenates used for the assay.
BOC Sciences' research and development pipeline of deuterated drugs has also been deployed in related targets of ophthalmic diseases, such as glaucoma, ocular hypertension, age-related macular degeneration and other related targets. Based on the company's DCL™ technology platform, BOC Sciences is able to develop preclinical candidate compound molecules targeting ophthalmic disease targets.
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BOC Sciences has always regarded intellectual property as the most valuable asset of the company and its customers. We have signed non-disclosure agreements with customers and employees before the project starts, and provide synthetic route design and synthesis services in strict accordance with the terms of the non-disclosure agreement, striving to provide customers with target compounds in the shortest time possible.